Skip to main content

Advertisement

SpringerLink
Log in

Validity of eleven prognostic scores with respect to intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Introduction

Tumor recurrence is the most frequent cause of death after liver transplantation for hepatocellular carcinoma. We selected ten other prognostic classifications to evaluate their potential to predict the risk of recurrence after LT for HCC as compared to the Milan classification. All of the other scores have not been compared with one another in a single cohort.

Methods

Data of 147 consecutive patients transplanted at our department between 1996 and 2014 were analyzed and staged for morphological and functional scores of underlying liver disease. For long-term follow-up, we analyzed intrahepatic (within the liver ± distant metastases) and extrahepatic (distant metastases only) recurrence separately.

Results and conclusions

The median survival time for all patients was 106 months. The 5- and 10-year observed survival rates were 61 and 43%, respectively. The observed cumulative 5- and 10-year recurrence rates were 37 and 39%, respectively, 10-year intrahepatic and extrahepatic recurrence rates were 12 and 27%, respectively. Median survival time after diagnosis of first recurrence was 7.5 (0–120) months; 2 and 18 months for all, intra- and extrahepatic recurrence, respectively. UCSF-, up to seven-, Shanghai Fudan- or Duvoux classifications can identify patients with a cumulative 10-year recurrence rate below 20%. The pre-therapeutic AFP level should be considered in addition to the geometry of the intrahepatic lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Agopian VG, Harlander-Locke M, Zarrinpar A, Kaldas FM, Farmer DG, Yersiz H, Finn RS, Tong M, Hiatt JR, Busuttil RW (2015) A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients. J Am Coll Surg 220(4):416–427. doi:10.1016/j.jamcollsurg.2014.12.025

    Article  PubMed  Google Scholar 

  • Andreou A, Gul S, Pascher A, Schoning W, Al-Abadi H, Bahra M, Klein F, Denecke T, Strucker B, Puhl G, Pratschke J, Seehofer D (2015) Patient and tumour biology predict survival beyond the Milan criteria in liver transplantation for hepatocellular carcinoma. HPB 17(2):168–175. doi:10.1111/hpb.12345

    Article  PubMed  Google Scholar 

  • Andreou A, Bahra M, Schmelzle M, Sucher R, Sauer IM, Guel-Klein S, Struecker B, Eurich D, Klein F, Pascher A, Pratschke J, Seehofer D (2016) Predictive factors for extrahepatic recurrence of hepatocellular carcinoma following liver transplantation. Clin Transplant. doi:10.1111/ctr.12755

    Google Scholar 

  • Bodzin AS, Lunsford KE, Markovic D, Harlander-Locke MP, Busuttil RW, Agopian VG (2016) Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation: impact of treatment modality and recurrence characteristics. Ann Surg. doi:10.1097/SLA.0000000000001894

    Google Scholar 

  • Capuano G, Daniele B, Gaeta GB, Gallo C, Perrone F (1998) A new prognostic system for hepatocellular carcinoma: a retrospective study of 435 patients: the Cancer of the Liver Italian Program (CLIP) investigators. Hepatology 28(3):751–755. doi:10.1002/hep.510280322

    Article  Google Scholar 

  • Chaiteerakij R, Zhang X, Addissie BD, Mohamed EA, Harmsen WS, Theobald PJ, Peters BE, Balsanek JG, Ward MM, Giama NH, Moser CD, Oseini AM, Umeda N, Venkatesh S, Harnois DM, Charlton MR, Yamada H, Satomura S, Algeciras-Schimnich A, Snyder MR, Therneau TM, Roberts LR (2015) Combinations of biomarkers and Milan criteria for predicting hepatocellular carcinoma recurrence after liver transplantation. Liver Transpl 21(5):599–606. doi:10.1002/lt.24117

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan KM, Yu MC, Chou HS, Wu TJ, Lee CF, Lee WC (2011) Significance of tumor necrosis for outcome of patients withhepatocellular carcinoma receiving locoregional therapy prior to liver transplantation. Ann Surg Oncol 18(9):2638–2646. doi:10.1245/s10434-011-1779-z

    Article  PubMed  Google Scholar 

  • Chapman WC, Majella Doyle MB, Stuart JE, Vachharajani N, Crippin JS, Anderson CD, Lowell JA, Shenoy S, Darcy MD, Brown DB (2008) Outcomes of neoadjuvant transarterial chemoembolization to downstage hepatocellular carcinoma before liver transplantation. Ann Surg 248(4):617–625. doi:10.1097/SLA.0b013e31818a07d4

    PubMed  Google Scholar 

  • Child CG, Turcotte JG (1964) Surgery and portal hypertension. Major Probl Clin Surg 1:1–85

    CAS  PubMed  Google Scholar 

  • Chok KS, Chan SC, Cheung TT, Chan AC, Fan ST, Lo CM (2011) Late recurrence of hepatocellular carcinoma after liver transplantation. World J Surg 35(9):2058–2062. doi:10.1007/s00268-011-1146-z

    Article  PubMed  PubMed Central  Google Scholar 

  • Clavien PA, Lesurtel M, Bossuyt PM, Gores GJ, Langer B, Perrier A (2012) Recommendations for liver transplantation for hepatocellular carcinoma: an international consensus conference report. Lancet Oncol 13(1):e11–e22. doi:10.1016/S1470-2045(11)70175-9

    Article  PubMed  Google Scholar 

  • Croome KP, Lee DD, Burns JM, Musto K, Paz D, Nguyen JH, Perry DK, Harnois DM, Taner CB (2015) The use of donation after cardiac death allografts does not increase recurrence of hepatocellular carcinoma. Am J Transplant 15(10):2704–2711. doi:10.1111/ajt.13306

    Article  CAS  PubMed  Google Scholar 

  • de’Angelis N, Landi F, Carra MC, Azoulay D (2015) Managements of recurrent hepatocellular carcinoma after liver transplantation: a systematic review. World J Gastroenterol 21(39):11185–11198. doi:10.3748/wjg.v21.i39.11185

    Article  PubMed  PubMed Central  Google Scholar 

  • Decaens T, Roudot-Thoraval F, Bresson-Hadni S, Meyer C, Gugenheim J, Durand F, Bernard PH, Boillot O, Compagnon P, Calmus Y, Hardwigsen J, Ducerf C, Pageaux GP, Dharancy S, Chazouilleres O, Cherqui D, Duvoux C (2006) Role of immunosuppression and tumor differentiation in predicting recurrence after liver transplantation for hepatocellular carcinoma: a multicenter study of 412 patients. World J Gastroenterol 12(45):7319–7325

    Article  PubMed  PubMed Central  Google Scholar 

  • Duvoux C, Roudot-Thoraval F, Decaens T, Pessione F, Badran H, Piardi T, Francoz C, Compagnon P, Vanlemmens C, Dumortier J, Dharancy S, Gugenheim J, Bernard PH, Adam R, Radenne S, Muscari F, Conti F, Hardwigsen J, Pageaux GP, Chazouilleres O, Salame E, Hilleret MN, Lebray P, Abergel A, Debette-Gratien M, Kluger MD, Mallat A, Azoulay D, Cherqui D (2012) Liver transplantation for hepatocellular carcinoma: a model including alpha-fetoprotein improves the performance of Milan criteria. Gastroenterology 143(4):986–994. doi:10.1053/j.gastro.2012.05.052 (quiz e914-985)

    Article  CAS  PubMed  Google Scholar 

  • Escartin A, Sapisochin G, Bilbao I, Vilallonga R, Bueno J, Castells L, Dopazo C, Castro E, Caralt M, Balsells J (2007) Recurrence of hepatocellular carcinoma after liver transplantation. Transpl Proc 39(7):2308–2310. doi:10.1016/j.transproceed.2007.06.042

    Article  CAS  Google Scholar 

  • Fan J, Zhou J, Xu Y, Qiu SJ, Wu ZQ, Yu Y, Huang XW, Tang ZY, Wang YQ (2006) Indication of liver transplantation for hepatocellular carcinoma: Shanghai Fudan Criteria. Zhonghua yi Xue Za Zhi 86(18):1227–1231

    PubMed  Google Scholar 

  • Hameed B, Mehta N, Sapisochin G, Roberts JP, Yao FY (2014) Alpha-fetoprotein level >1000 ng/mL as an exclusion criterion for liver transplantation in patients with hepatocellular carcinoma meeting the Milan criteria. Liver Transpl 20(8):945–951. doi:10.1002/lt.23904

    Article  PubMed  PubMed Central  Google Scholar 

  • Herrero JI, Sangro B, Pardo F, Quiroga J, Inarrairaegui M, Rotellar F, Montiel C, Alegre F, Prieto J (2008) Liver transplantation in patients with hepatocellular carcinoma across Milan criteria. Liver Transpl 14(3):272–278. doi:10.1002/lt.21368

    Article  PubMed  Google Scholar 

  • Hwang S, Kim YH, Kim DK, Ahn CS, Moon DB, Kim KH, Ha TY, Song GW, Jung DH, Kim HR, Park GC, Namgoong JM, Yoon SY, Jung SW, Park SI, Lee SG (2012) Resection of pulmonary metastases from hepatocellular carcinoma following liver transplantation. World J Surg 36(7):1592–1602. doi:10.1007/s00268-012-1533-0

    Article  PubMed  Google Scholar 

  • Kornberg A, Kupper B, Tannapfel A, Katenkamp K, Thrum K, Habrecht O, Wilberg J (2010) Long-term survival after recurrent hepatocellular carcinoma in liver transplant patients: clinical patterns and outcome variables. Eur J Surg Oncol 36(3):275–280. doi:10.1016/j.ejso.2009.10.001

    Article  CAS  PubMed  Google Scholar 

  • Lee SG, Hwang S, Moon DB, Ahn CS, Kim KH, Sung KB, Ko GY, Park KM, Ha TY, Song GW (2008) Expanded indication criteria of living donor liver transplantation for hepatocellular carcinoma at one large-volume center. Liver Transpl 14(7):935–945. doi:10.1002/lt.21445

    Article  PubMed  Google Scholar 

  • Llovet JM, Bru C, Bruix J (1999) Prognosis of hepatocellular carcinoma: the BCLC staging classification. Semin Liver Dis 19(3):329–338. doi:10.1055/s-2007-1007122

    Article  CAS  PubMed  Google Scholar 

  • Marangoni G, Faraj W, Sethi H, Rela M, Muiesan P, Heaton N (2008) Liver resection in liver transplant recipients. Hepatobiliary Pancreat Dis Int HBPD INT 7(6):590–594

    PubMed  Google Scholar 

  • Mazzaferro V, Regalia E, Doci R, Andreola S, Pulvirenti A, Bozzetti F, Montalto F, Ammatuna M, Morabito A, Gennari L (1996) Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334(11):693–699. doi:10.1056/NEJM199603143341104

    Article  CAS  PubMed  Google Scholar 

  • Mazzaferro V, Llovet JM, Miceli R, Bhoori S, Schiavo M, Mariani L, Camerini T, Roayaie S, Schwartz ME, Grazi GL, Adam R, Neuhaus P, Salizzoni M, Bruix J, Forner A, De Carlis L, Cillo U, Burroughs AK, Troisi R, Rossi M, Gerunda GE, Lerut J, Belghiti J, Boin I, Gugenheim J, Rochling F, Van Hoek B, Majno P (2009) Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis. Lancet Oncol 10(1):35–43. doi:10.1016/S1470-2045(08)70284-5

    Article  PubMed  Google Scholar 

  • Millonig G, Graziadei IW, Freund MC, Jaschke W, Stadlmann S, Ladurner R, Margreiter R, Vogel W (2007) Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 13(2):272–279. doi:10.1002/lt.21033

    Article  PubMed  Google Scholar 

  • Na GH, Hong TH, You YK, Kim DG (2016) Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation. World J Gastroenterol 22(25):5790–5799. doi:10.3748/wjg.v22.i25.5790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okuda K, Ohtsuki T, Obata H, Tomimatsu M, Okazaki N, Hasegawa H, Nakajima Y, Ohnishi K (1985) Natural history of hepatocellular carcinoma and prognosis in relation to treatment. Study of 850 patients. Cancer 56(4):918–928

    Article  CAS  PubMed  Google Scholar 

  • Otto G, Herber S, Heise M, Lohse AW, Monch C, Bittinger F, Hoppe-Lotichius M, Schuchmann M, Victor A, Pitton M (2006) Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma. Liver Transpl 12(8):1260–1267. doi:10.1002/lt.20837

    Article  PubMed  Google Scholar 

  • Parfitt JR, Marotta P, Alghamdi M, Wall W, Khakhar A, Suskin NG, Quan D, McAllister V, Ghent C, Levstik M, McLean C, Chakrabarti S, Garcia B, Driman DK (2007) Recurrent hepatocellular carcinoma after transplantation: use of apathological score on explanted livers to predict recurrence. Liver Transpl 13(4):543–551. doi:10.1002/lt.21078

    Article  PubMed  Google Scholar 

  • Pecchi A, Besutti G, De Santis M, Del Giovane C, Nosseir S, Tarantino G, Di Benedetto F, Torricelli P (2015) Post-transplantation hepatocellular carcinoma recurrence: patterns and relation between vascularity and differentiation degree. World J Hepatol 7(2):276–284. doi:10.4254/wjh.v7.i2.276

    Article  PubMed  PubMed Central  Google Scholar 

  • Ravaioli M, Grazi GL, Piscaglia F, Trevisani F, Cescon M, Ercolani G, Vivarelli M, Golfieri R, D’Errico Grigioni A, Panzini I, Morelli C, Bernardi M, Bolondi L, Pinna AD (2008) Liver transplantation for hepatocellular carcinoma: results of down-staging in patients initially outside the Milan selection criteria. Am J Transplant 8(12):2547–2557. doi:10.1111/j.1600-6143.2008.02409.x

    Article  CAS  PubMed  Google Scholar 

  • Roayaie S, Schwartz JD, Sung MW, Emre SH, Miller CM, Gondolesi GE, Krieger NR, Schwartz ME (2004) Recurrence of hepatocellular carcinoma after liver transplant: patterns and prognosis. Liver Transpl 10(4):534–540. doi:10.1002/lt.20128

    Article  PubMed  Google Scholar 

  • Sapisochin G, Goldaracena N, Astete S, Laurence JM, Davidson D, Rafael E, Castells L, Sandroussi C, Bilbao I, Dopazo C, Grant DR, Lazaro JL, Caralt M, Ghanekar A, McGilvray ID, Lilly L, Cattral MS, Selzner M, Charco R, Greig PD (2015) Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series. Ann Surg Oncol 22(7):2286–2294. doi:10.1245/s10434-014-4273-6

    Article  CAS  PubMed  Google Scholar 

  • Sapisochin G, Goldaracena N, Laurence JM, Dib M, Barbas A, Ghanekar A, Cleary SP, Lilly L, Cattral MS, Marquez M, Selzner M, Renner E, Selzner N, McGilvray ID, Greig PD, Grant DR (2016) The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: a prospective validation study. Hepatology. doi:10.1002/hep.28643

    Google Scholar 

  • Schlitt HJ, Neipp M, Weimann A, Oldhafer KJ, Schmoll E, Boeker K, Nashan B, Kubicka S, Maschek H, Tusch G, Raab R, Ringe B, Manns MP, Pichlmayr R (1999) Recurrence patterns of hepatocellular and fibrolamellar carcinoma after liver transplantation. J Clin Oncol 17(1):324–331

    Article  CAS  PubMed  Google Scholar 

  • Schraiber LS, de Mattos AA, Zanotelli ML, Cantisani GP, Brandao AB, Marroni CA, Kiss G, Ernani L, Marcon Pdos S (2016) Alpha-fetoprotein Level predicts recurrence after transplantation in hepatocellular carcinoma. Medicine 95(3):e2478. doi:10.1097/MD.0000000000002478

    Article  CAS  PubMed Central  Google Scholar 

  • Schwartz M, Roayaie S, Llovet J (2005) How should patients with hepatocellular carcinoma recurrence after liver transplantation be treated? J Hepatol 43(4):584–589. doi:10.1016/j.jhep.2005.07.019

    Article  PubMed  Google Scholar 

  • Seehofer D, Nebrig M, Denecke T, Kroencke T, Weichert W, Stockmann M, Somasundaram R, Schott E, Puhl G, Neuhaus P (2012) Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis. Clin Transplant 26(5):764–774. doi:10.1111/j.1399-0012.2012.01609.x

    Article  PubMed  Google Scholar 

  • Sobin LH, Gospodarowicz MK, Wittekind C, International Union against Cancer (2010) TNM classification of malignant tumours, 7th edn. Wiley, Chichester, Hoboken

    Google Scholar 

  • Sotiropoulos GC, Lang H, Nadalin S, Neuhauser M, Molmenti EP, Baba HA, Paul A, Saner FH, Weber F, Hilgard P, Frilling A, Broelsch CE, Malago M (2007) Liver transplantation for hepatocellular carcinoma: University Hospital Essen experience and metaanalysis of prognostic factors. J Am Coll Surg 205(5):661–675. doi:10.1016/j.jamcollsurg.2007.05.023

    Article  PubMed  Google Scholar 

  • Taketomi A, Fukuhara T, Morita K, Kayashima H, Ninomiya M, Yamashita Y, Ikegami T, Uchiyama H, Yoshizumi T, Soejima Y, Shirabe K, Maehara Y (2010) Improved results of a surgical resection for the recurrence of hepatocellular carcinoma after living donor liver transplantation. Ann Surg Oncol 17(9):2283–2289. doi:10.1245/s10434-010-0999-y

    Article  PubMed  Google Scholar 

  • Toso C, Trotter J, Wei A, Bigam DL, Shah S, Lancaster J, Grant DR, Greig PD, Shapiro AM, Kneteman NM (2008) Total tumor volume predicts risk of recurrence following liver transplantation in patients with hepatocellular carcinoma. Liver Transpl 14(8):1107–1115. doi:10.1002/lt.21484

    Article  PubMed  Google Scholar 

  • Valdivieso A, Bustamante J, Gastaca M, Uriarte JG, Ventoso A, Ruiz P, Fernandez JR, Pijoan I, Testillano M, Suarez MJ, Montejo M, Ortiz de Urbina J (2010) Management of hepatocellular carcinoma recurrence after liver transplantation. Transpl Proc 42(2):660–662. doi:10.1016/j.transproceed.2010.02.014

    Article  CAS  Google Scholar 

  • Varona MA, Soriano A, Aguirre-Jaime A, Garrido S, Oton E, Diaz D, Portero J, Bravo P, Barrera MA, Perera A (2015) Risk factors of hepatocellular carcinoma recurrence after liver transplantation: accuracy of the alpha-fetoprotein model in a single-center experience. Transpl Proc 47(1):84–89. doi:10.1016/j.transproceed.2014.12.013

    Article  CAS  Google Scholar 

  • Verduijn M, Grootendorst DC, Dekker FW, Jager KJ, le Cessie S (2011) The analysis of competing events like cause-specific mortality–beware of the Kaplan–Meier method. Nephrol Dial Transplant 26(1):56–61. doi:10.1093/ndt/gfq661

    Article  PubMed  Google Scholar 

  • Vibert E, Azoulay D, Hoti E, Iacopinelli S, Samuel D, Salloum C, Lemoine A, Bismuth H, Castaing D, Adam R (2010) Progression of alphafetoprotein before liver transplantation for hepatocellular carcinoma in cirrhotic patients: a critical factor. Am J Transplant 10(1):129–137. doi:10.1111/J.1600-6143.2009.02750.X

    Article  CAS  PubMed  Google Scholar 

  • Yao FY, Ferrell L, Bass NM, Watson JJ, Bacchetti P, Venook A, Ascher NL, Roberts JP (2001) Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 33(6):1394–1403. doi:10.1053/jhep.2001.24563

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Li C, Wen T, Yan L, Li B, Yang J, Wang W, Xu M, Lu W, Jiang L (2015) Appropriate treatment strategies for intrahepatic recurrence after curative resection of hepatocellular carcinoma initially within the Milan criteria: according to the recurrence pattern. Eur J Gastroenterol Hepatol 27(8):933–940. doi:10.1097/MEG.0000000000000383

    Article  PubMed  Google Scholar 

  • Zheng SS, Xu X, Wu J, Chen J, Wang WL, Zhang M, Liang TB, Wu LM (2008) Liver transplantation for hepatocellular carcinoma: Hangzhou experiences. Transplantation 85(12):1726–1732. doi:10.1097/TP.0b013e31816b67e4

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General, Visceral and Vascular Surgery, University Hospital Jena, Erlanger Allee 104, 07743, Jena, Germany

    A. Bauschke, A. Altendorf-Hofmann, H. Kissler, A. Koch, C. Malessa & U. Settmacher

Authors
  1. A. Bauschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Altendorf-Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Kissler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. Malessa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. U. Settmacher
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Bauschke.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical standard

The retrospective study was in accordance with the ethical standards of the Helsinki Declaration.

Informed consent

All patients give their consent for registration in the tumor registry. We have only used data from the clinical data registry.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bauschke, A., Altendorf-Hofmann, A., Kissler, H. et al. Validity of eleven prognostic scores with respect to intra- and extrahepatic recurrence of hepatocellular carcinoma after liver transplantation. J Cancer Res Clin Oncol 143, 2595–2605 (2017). https://doi.org/10.1007/s00432-017-2507-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-017-2507-2

Keywords

Search

Navigation